SYNVISC
Report
- Report Number
- 2246315-2025-00037
- Event Type
- Injury
- Date Received
- September 18, 2025
- Report Date
- November 3, 2025
- Manufacturer
- GENZYME CORPORATION(RIDGEFIELD)
- Product Code
- MOZ
- Report Source
- Manufacturer report
- Reporter Location
- RS
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
- Health Professional
- Yes
Narratives
SANOFI COMPANY COMMENT DATED 16-SEP-2025: THIS CASE INVOLVES A 59 YEARS OLD FEMALE PATIENT WHO EXPERIENCED CHRONIC HYALURONAN-RELATED OSTEOMYELITIS WHILE BEING TREATED WITH SYNVISC. BASED ON THE INFORMATION RECEIVED REGARDING THIS CASE, THE CAUSAL ROLE OF THE COMPANY SUSPECT PRODUCT CANNOT BE EXCLUDED IN THE OCCURRENCE OF THE EVENT DUE TO COMPATIBLE TEMPORAL RELATIONSHIP OF ADVERSE DRUG REACTION (ADR) TO THE DRUG. PATIENT UNDERLYING CONDITION END-STAGE SEVERE KNEE OA (OSTEOARTHRITIS) CAN BE CONFOUNDER FOR THE SAME. ALSO LACK OF INFORMATION REGARDING PAST AND CONCOMITANT DRUGS, THERAPY DETAILS AND LATENCY TO ONSET PRECLUDES A COMPREHENSIVE ASSESSMENT IN THIS CASE.
CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS [ASEPTIC NECROSIS OF BONE], CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS [SYNOVITIS CHRONIC], CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS [FOREIGN BODY GRANULOMA], FUNCTIONAL IMPAIRMENT [GAIT DISTURBANCE], PERSISTENT CHRONIC PAIN [ARTHRALGIA], FAILURE OF CONSERVATIVE TREATMENT [DEVICE INEFFECTIVE]. CASE NARRATIVE: INTRA-ARTICULAR HYALURONAN INJECTIONS REPRESENT A WIDELY USED AND GENERALLY SAFE THERAPEUTIC APPROACH FOR KNEE OSTEOARTHRITIS (OA). HOWEVER, THE SIDE EFFECTS OF THIS TREATMENT REMAIN INSUFFICIENTLY STUDIED. ACUTE POST-INJECTION REACTIONS, PARTICULARLY THOSE ARISING FROM AN IMPROPER TECHNIQUE RESULTING IN THE DEPOSITION OF THE THERAPEUTIC AGENT INTO JOINT TISSUES, ARE WELL-DOCUMENTED. IN CONTRAST, CHRONIC HYALURONAN-INDUCED INFLAMMATORY RESPONSES HAVE RECEIVED SCANT ATTENTION IN THE SCIENTIFIC LITERATURE. THE AIM OF THIS STUDY IS TO CHARACTERIZE FOR THE FIRST TIME THE MORPHOLOGICAL PATTERNS OF CHRONIC GRANULOMATOUS INFLAMMATION INDUCED BY EXOGENOUS HYALURONAN (E-HA) IN OSTEOARTHRITIC KNEES, FOCUSING ON THREE DISTINCT TISSUE REACTIONS: SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS. USING A THREE-CASE SERIES APPROACH AND MORPHOLOGICAL ANALYSIS, WE IDENTIFIED E-HA PENETRATION PATHWAYS; DESCRIBED ASSOCIATED FOREIGN BODY RESPONSES IN THE SYNOVIAL, ADIPOSE, AND BONE TISSUES OF THE JOINTS; AND EMPHASIZED THE CLINICAL RELEVANCE OF THESE UNDERREPORTED ADVERSE EFFECTS. THESE OBSERVATIONS HIGHLIGHT AN UNDERSTUDIED PHENOMENONAN ACTIVE CONFLICT BETWEEN E-HA AND JOINT TISSUES THAT RECOGNIZE IT AS A FOREIGN BODY. THE PREVALENCE, CLINICAL SIGNIFICANCE, AND PROGNOSTIC IMPLICATIONS OF THIS PHENOMENON REQUIRE FURTHER INVESTIGATION. INITIAL INFORMATION RECEIVED ON 10-SEP-2025 BY HEALTH CARE PROFESSIONAL REGARDING AN UNSOLICITED VALID SERIOUS CASE ISSUED FROM A LITERATURE ARTICLE: LYALINA V, ESHMOTOVA G, KARAVAN A, KORSHUNOV A, ZAROV A, BONARTSEV A ET AL. HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS IN THE OSTEOARTHRITIC KNEE: A MORPHOLOGICAL CASE SERIES OF THREE PATIENTS. INT J MOL SCI. 2025;26(16):1-14. AVAILABLE FROM: HTTPS://DOI.ORG/10.3390/IJMS26168073. FROM THIS PUBLICATION SEVERAL CLUSTERS WERE CREATED. THIS CASE INVOLVES A 59-YEAR-OLD FEMALE PATIENT WHO EXPERIENCED CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS (OSTEONECROSIS) (FOREIGN BODY REACTION) AND CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS (SYNOVITIS), PERSISTENT CHRONIC PAIN (ARTHRALGIA), FUNCTIONAL IMPAIRMENT (GAIT DISTURBANCE) AND FAILURE OF CONSERVATIVE TREATMENT (DEVICE INEFFECTIVE) WHILE BEING TREATED WITH SYNVISC (LATENCY: UNKNOWN). THE PATIENT'S PAST MEDICAL TREATMENT(S), VACCINATION(S) AND FAMILY HISTORY WERE NOT PROVIDED. PATIENT HAD END-STAGE SEVERE KNEE OA (OSTEOARTHRITIS). FOR SEVERAL YEARS PRIOR TO SURGERY, PATIENTS HAD RECEIVED MULTIPLE INTRA-ARTICULAR INJECTIONS OF VARIOUS (UNSPECIFIED E-HA (EXOGENOUS HYALURONAN) PREPARATIONS (DOSE, FREQUENCY, LOT/BATCH NUMBER AND EXPIRY DATE: UNSPECIFIED). AN UNSPECIFIED TIME LATER, ON AN UNKNOWN DATE, PATIENT EXPERIENCED CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS AND CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS. AREOLAR AND FIBOUS SYNOVIAL MEMBRANE AND SUBCHONDRAL BONE TISSUE SAMPLES WERE AVAILABLE FOR EXAMINATION. PATIENT PRESENTED WITH PERSISTENT CHRONIC PAIN SYNDROME, SIGNIFICANT FUNCTIONAL IMPAIRMENT, AND FAILURE OF CONSERVATIVE TREATMENT. PATIENT UNDERWENT KNEE ARTHROPLASTY FOR END-STAGE SEVERE OA. ACTION TAKEN: UNKNOWN FOR ALL EVENTS. CORRECTIVE TREATMENT: NOT REPORTED FOR OSTEONECROSIS, FOREIGN BODY REACTION, SYNOVITIS, ARTHRALGIA AND GAIT DISTURBANCE. OUTCOME: UNKNOWN FOR OSTEONECROSIS, FOREIGN BODY REACTION, SYNOVITIS, ARTHRALGIA AND GAIT DISTURBANCE. SERIOUSNESS CRITERIA: MEDICALLY SIGNIFICANT FOR OSTEOMYELITIS CHRONIC; NON-SERIOUS FOR OTHER EVENTS. REPORTER CAUSALITY: RELATED FOR ALL EVENTS. A PRODUCT TECHNICAL COMPLAINT (PTC) WAS INITIATED ON 19-SEP-2025 FOR SYNVISC (LOT/BATCH NUMBER: UNKNOWN) WITH GLOBAL PTC NUMBER: COMPLAINT: (B)(4) THE PTC STATED: THE INCIDENT DESCRIPTION, THE INVESTIGATION URGENCY HAS BEEN CONFIRMED AS STANDARD. PER THE PRODUCT-SPECIFIC COMPLAINT CODES FOR "SYNVISC ", AND THE INCIDENT DESCRIPTION, THE DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT" HAS BEEN ASSIGNED TO THIS INVESTIGATION. THE INVESTIGATION URGENCY, QEE/QDN DECISION AND DEFECT CODE MAY CHANGE BASED ON THE OUTCOME OF THE INVESTIGATION. THE MINIMUM INVESTIGATION REQUIREMENTS FOR DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT INCLUDES PRODUCT EVENT HISTORY REVIEW, LOT HISTORY REVIEW, QA BATCH/MANUFACTURING REVIEW (INCLUDING API), THE RESULTS OF THESE REVIEWS ARE SUMMARIZED BELOW: PRODUCT EVENT HISTORY REVIEW: ATTACHMENT 01- COMET PRODUCT (SYNVISC) EVENT HISTORY REPORT FOR THE PAST TWO YEARS WAS GENERATED ON 13-OCT-2025 AND SHOWED 56 COMPLAINTS RELATED TO DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT". ALL THE COMPLAINTS WERE CONCLUDED AS "NO ASSESSMENT POSSIBLE". PRODUCT (SYNVISC) EVENT HISTORY REPORT FOR THE PAST TWO YEARS WAS GENERATED ON 13-OCT-2025 AND SHOWED 166 COMPLAINTS RELATED TO "OTHER PHARMACOVIGILANCE EVENT" (INCLUDING CURRENT COMPLAINT). AMONG THESE "7 COMPLAINTS (INCLUDING CURRENT COMPLAINT) ARE IN OPEN STATE (INVESTIGATION ONGOING) "REVIEW OF EVENT HISTORY REPORT INFERS THAT THERE IS NO CONFIRM COMPLAINT IDENTIFIED, WHICH INCLUDES EVENT IS LINKED TO A FAILURE OR THAT THE DEFECT IS RELATED TO THE PRODUCT OR MANUFACTURING PROCESS. LOT HISTORY REVIEW: AS THE BATCH NUMBER IS UNKNOWN, LOT HISTORY REVIEW AND ASSESSMENT IS NOT POSSIBLE. COMPLAINT SAMPLE EVALUATION: COMPLAINT SAMPLE IS NOT AVAILABLE. HENCE ASSESSMENT IS NOT APPLICABLE. INVESTIGATION OUTCOME: THERE IS NO QUALITY RELATED DEFECT THAT WOULD ATTRIBUTE TO A MALFUNCTION A DEATH OR SERIOUS INJURY. MAH PHARMACOVIGILANCE CONTINUOUSLY MONITORS ADVERSE EVENT REPORTS WITH OR WITHOUT LOT NUMBER, AND ASSESSES POSSIBLE ASSOCIATIONS WITH THEIR CORRESPONDING PRODUCT LOT, AS A PART OF ROUTINE SAFETY SURVEILLANCE EFFORT TO DETECT SAFETY SIGNALS. AS THE PRODUCT LOT NUMBER IS NOT AVAILABLE, A BATCH RECORD REVIEW AND ASSESSMENT IS NOT POSSIBLE. DUE LACK OF INFORMATION, NO ASSESSMENT IS POSSIBLE. CONTROLS IN PLACE: PRIOR TO BATCH RELEASE, REVIEW OF ALL FINISHED BATCH RECORDS FOR SPECIFICATION CONFORMANCE WILL BE PERFORMED. IF ANY OUT OF SPECIFICATION RESULT IS IDENTIFIED, IT IS MITIGATED THROUGH THE PROCEDURE FOR NONCONFORMING MATERIAL OR PRODUCT PROCESS. ADVERSE EVENTS WILL BE MONITORED BY THE MAH (MARKETING AUTHORISATION HOLDER) HOLDER. TREND ANALYSIS WILL BE PERFORMED ON A PERIODIC BASIS. TO DETERMINE IF A (CORRECTIVE ACTION AND PREVENTIVE ACTION) IS REQUIRED FOR DEFINED PROCEDURES. TREND ANALYSIS: PER QU-WIN-0056595, IF THE NUMBER OF COMPLAINTS IS = 10 CONFIRMED COMPLAINTS WITH THE SAME DEFECT CODE FOR THE IMPLICATED PRODUCT IT INDICATES A POTENTIAL TREND FOR THE ASSIGNED DEFECT TYPE. A CONFIRMED COMPLAINT IS ONE WHERE THE INVESTIGATION HAS CONCLUDED THAT THE REPORTED EVENT IS LINKED TO A FAILURE OR THAT THE DEFECT IS RELATED TO THE PRODUCT OR MANUFACTURING PROCESS. A REVIEW OF THE PRODUCT EVENT HISTORY REVEALS THAT 222 COMPLAINTS INCLUDING THE CURRENT COMPLAINT FOR PRODUCT SYNVISC WITH DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT" HOWEVER, REVIEW OF INVESTIGATION CONCLUSIONS INFERS THAT THERE IS NO CONFIRM COMPLAINT IDENTIFIED FOR THE PRODUCT SYNVISC WITH DEFECT "OTHER PHARMACOVIGILANCE EVENT" AND INDICATES THAT NO POTENTIAL TREND (N = 10) EXISTS. CONSIDERING THE ABOVE FURTHER TREND ANALYSIS OF THE PRODUCT BASED ON THE QUARTERLY DATA IS NOT WARRANTED. CONCLUSION: BASED ON INVESTIGATION OUTCOME, NO QEE WAS OPENED. THE INVESTIGATION URGENCY IS CONFORMED AS STANDARD. AS THE BATCH NUMBER IS NOT AVAILABLE FOR SUBJECT COMPLAINT, NO ASSESSMENT IS POSSIBLE. HENCE INVESTIGATION CONCLUSION IS SELECTED AS "NO ASSESSMENT POSSIBLE" WITH CAUSE CODE AS "UNDETERMINED CAUSE" SANOFI EM&S GEN MED VACCINES QUALITY TEAM WILL CONTINUE TO MONITOR AND TREND THESE TYPES OF EVENTS AND WORK WITH THE CMO(S) TO INITIATE CORRECTIVE AND/OR PREVENTIVE ACTIONS AS NECESSARY. IF ADDITIONAL INFORMATION BECOMES AVAILABLE FOR THIS COMPLAINT, THE INVESTIGATION WILL BE REOPENED AND RE-EVALUATED. THE FINAL PTC WAS COMPLETED ON 13-OCT-2025 WITH SUMMARIZED CONCLUSION AS NO ASSESSMENT POSSIBLE. THE FINAL PTC WAS COMPLETED ON 13-OCT-2025 WITH SUMMARIZED CONCLUSION AS NO ASSESSMENT POSSIBLE. NOTE: PATIENT RECEIPT OF INTRA-ARTICULAR EXOGENOUS HYALURONAN INJECTION. NO EXOGENOUS HYALURONAN BRAND NAME WAS REPORTED; IT IS CAPTURED UNDER THE BRAND SYNVISC IN A CONSERVATIVE APPROACH. ADDITIONAL INFORMATION WAS RECEIVED ON 13-OCT-2025 FROM AFFILIATE AND FOLLOWING CHANGES MADE: PTC RESULT ADDED AND NARRATIVE AMENDED ACCORDINGLY. BASED ON PREVIOUSLY REPORTED INFORMATION WITH CSD 10-SEP-2025, A SIGNIFICANT AMENDMENT HAS BEEN PERFORMED ON 17-OCT-2025 AND THE FOLLOWING CHANGES WERE AMENDED: EVENT CODING ADDED FOR CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS: FOREIGN BODY GRANULOMA (LLT) (PT: FOREIGN BODY REACTION) AND ASEPTIC NECROSIS OF BONE (LLT) (PT: OSTEONECROSIS). BASED ON INFORMATION PREVIOUSLY RECEIVED ON CSD 13-OCT-2025, A SIGNIFICANT AMENDMENT HAS BEEN PERFORMED ON 03-NOV-2025 AND THE FOLLOWING CHANGES WERE AMENDED: EVENTS PERSISTENT CHRONIC PAIN (KNEE PAIN; PT: ARTHRALGIA), FUNCTIONAL IMPAIRMENT (PT: GAIT DISTURBANCE), AND FAILURE OF CONSERVATIVE TREATMENT (PT: DEVICE INEFFECTIVE) ADDED AND ANNEX CODE E FOR EVENT 'OSTEONECROSIS' IN IMDRF ADDED AND NARRATIVE AMENDED ACCORDINGLY.
CHRONIC HYALURONAN-RELATED OSTEOMYELITIS [CHRONIC OSTEOMYELITIS]. CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS [SYNOVITIS CHRONIC]. CASE NARRATIVE: INTRA-ARTICULAR HYALURONAN INJECTIONS REPRESENT A WIDELY USED AND GENERALLY SAFE THERAPEUTIC APPROACH FOR KNEE OSTEOARTHRITIS (OA). HOWEVER, THE SIDE EFFECTS OF THIS TREATMENT REMAIN INSUFFICIENTLY STUDIED. ACUTE POST-INJECTION REACTIONS, PARTICULARLY THOSE ARISING FROM AN IMPROPER TECHNIQUE RESULTING IN THE DEPOSITION OF THE THERAPEUTIC AGENT INTO JOINT TISSUES, ARE WELL-DOCUMENTED. IN CONTRAST, CHRONIC HYALURONAN-INDUCED INFLAMMATORY RESPONSES HAVE RECEIVED SCANT ATTENTION IN THE SCIENTIFIC LITERATURE. THE AIM OF THIS STUDY IS TO CHARACTERIZE FOR THE FIRST TIME THE MORPHOLOGICAL PATTERNS OF CHRONIC GRANULOMATOUS INFLAMMATION INDUCED BY EXOGENOUS HYALURONAN (E-HA) IN OSTEOARTHRITIC KNEES, FOCUSING ON THREE DISTINCT TISSUE REACTIONS: SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS. USING A THREE-CASE SERIES APPROACH AND MORPHOLOGICAL ANALYSIS, WE IDENTIFIED E-HA PENETRATION PATHWAYS; DESCRIBED ASSOCIATED FOREIGN BODY RESPONSES IN THE SYNOVIAL, ADIPOSE, AND BONE TISSUES OF THE JOINTS; AND EMPHASIZED THE CLINICAL RELEVANCE OF THESE UNDERREPORTED ADVERSE EFFECTS. THESE OBSERVATIONS HIGHLIGHT AN UNDERSTUDIED PHENOMENONAN ACTIVE CONFLICT BETWEEN E-HA AND JOINT TISSUES THAT RECOGNIZE IT AS A FOREIGN BODY. THE PREVALENCE, CLINICAL SIGNIFICANCE, AND PROGNOSTIC IMPLICATIONS OF THIS PHENOMENON REQUIRE FURTHER INVESTIGATION. INITIAL INFORMATION RECEIVED ON 10-SEP-2025 BY HEALTH CARE PROFESSIONAL REGARDING AN UNSOLICITED VALID SERIOUS CASE ISSUED FROM A LITERATURE ARTICLE: LYALINA V, ESHMOTOVA G, KARAVAN A, KORSHUNOV A, ZAROV A, BONARTSEV A ET AL. HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS IN THE OSTEOARTHRITIC KNEE: A MORPHOLOGICAL CASE SERIES OF THREE PATIENTS. INT J MOL SCI. 2025;26(16):1-14. AVAILABLE FROM: HTTPS://DOI.ORG/10.3390/IJMS26168073. FROM THIS PUBLICATION SEVERAL CLUSTERS WERE CREATED. THIS CASE INVOLVES A 59-YEAR-OLD FEMALE PATIENT WHO EXPERIENCED CHRONIC HYALURONAN-RELATED OSTEOMYELITIS (OSTEOMYELITIS CHRONIC) AND CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS (SYNOVITIS) WHILE BEING TREATED WITH SYNVISC (LATENCY: UNKNOWN). THE PATIENT'S PAST MEDICAL TREATMENT(S), VACCINATION(S) AND FAMILY HISTORY WERE NOT PROVIDED. PATIENT HAD END-STAGE SEVERE KNEE OA (OSTEOARTHRITIS). FOR SEVERAL YEARS PRIOR TO SURGERY, PATIENTS HAD RECEIVED MULTIPLE INTRA-ARTICULAR INJECTIONS OF VARIOUS (UNSPECIFIED E-HA (EXOGENOUS HYALURONAN) PREPARATIONS (DOSE, FREQUENCY, LOT/BATCH NUMBER AND EXPIRY DATE: UNSPECIFIED). AN UNSPECIFIED TIME LATER, ON AN UNKNOWN DATE, PATIENT EXPERIENCED CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS AND OSTEOMYELITIS. AREOLAR AND FIBOUS SYNOVIAL MEMBRANE AND SUBCHONDRAL BONE TISSUE SAMPLES WERE AVAILABLE FOR EXAMINATION. PATIENT PRESENTED WITH PERSISTENT CHRONIC PAIN SYNDROME, SIGNIFICANT FUNCTIONAL IMPAIRMENT, AND FAILURE OF CONSERVATIVE TREATMENT. PATIENT UNDERWENT KNEE ARTHROPLASTY FOR END-STAGE SEVERE OA. ACTION TAKEN: UNKNOWN FOR BOTH EVENTS. CORRECTIVE TREATMENT: NOT REPORTED FOR BOTH EVENTS. OUTCOME: UNKNOWN FOR BOTH EVENTS. SERIOUSNESS CRITERIA: MEDICALLY SIGNIFICANT FOR OSTEOMYELITIS CHRONIC; NON-SERIOUS FOR SYNOVITIS. REPORTER CAUSALITY: RELATED FOR BOTH EVENTS. NOTE: PATIENT RECEIPT OF INTRA-ARTICULAR EXOGENOUS HYALURONAN INJECTION. NO EXOGENOUS HYALURONAN BRAND NAME WAS REPORTED; IT IS CAPTURED UNDER THE BRAND SYNVISC IN A CONSERVATIVE APPROACH.
CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS [ASEPTIC NECROSIS OF BONE] CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS [SYNOVITIS CHRONIC] CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS [FOREIGN BODY GRANULOMA] CASE NARRATIVE: INTRA-ARTICULAR HYALURONAN INJECTIONS REPRESENT A WIDELY USED AND GENERALLY SAFE THERAPEUTIC APPROACH FOR KNEE OSTEOARTHRITIS (OA). HOWEVER, THE SIDE EFFECTS OF THIS TREATMENT REMAIN INSUFFICIENTLY STUDIED. ACUTE POST-INJECTION REACTIONS, PARTICULARLY THOSE ARISING FROM AN IMPROPER TECHNIQUE RESULTING IN THE DEPOSITION OF THE THERAPEUTIC AGENT INTO JOINT TISSUES, ARE WELL-DOCUMENTED. IN CONTRAST, CHRONIC HYALURONAN-INDUCED INFLAMMATORY RESPONSES HAVE RECEIVED SCANT ATTENTION IN THE SCIENTIFIC LITERATURE. THE AIM OF THIS STUDY IS TO CHARACTERIZE FOR THE FIRST TIME THE MORPHOLOGICAL PATTERNS OF CHRONIC GRANULOMATOUS INFLAMMATION INDUCED BY EXOGENOUS HYALURONAN (E-HA) IN OSTEOARTHRITIC KNEES, FOCUSING ON THREE DISTINCT TISSUE REACTIONS: SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS. USING A THREE-CASE SERIES APPROACH AND MORPHOLOGICAL ANALYSIS, WE IDENTIFIED E-HA PENETRATION PATHWAYS; DESCRIBED ASSOCIATED FOREIGN BODY RESPONSES IN THE SYNOVIAL, ADIPOSE, AND BONE TISSUES OF THE JOINTS; AND EMPHASIZED THE CLINICAL RELEVANCE OF THESE UNDERREPORTED ADVERSE EFFECTS. THESE OBSERVATIONS HIGHLIGHT AN UNDERSTUDIED PHENOMENONAN ACTIVE CONFLICT BETWEEN E-HA AND JOINT TISSUES THAT RECOGNIZE IT AS A FOREIGN BODY. THE PREVALENCE, CLINICAL SIGNIFICANCE, AND PROGNOSTIC IMPLICATIONS OF THIS PHENOMENON REQUIRE FURTHER INVESTIGATION.INITIAL INFORMATION RECEIVED ON 10-SEP-2025 BY HEALTH CARE PROFESSIONAL REGARDING AN UNSOLICITED VALID SERIOUS CASE ISSUED FROM A LITERATURE ARTICLE:LYALINA V, ESHMOTOVA G, KARAVAN A, KORSHUNOV A, ZAROV A, BONARTSEV A ET AL. HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS, ADIPOSITIS, AND OSTEOMYELITIS IN THE OSTEOARTHRITIC KNEE: A MORPHOLOGICAL CASE SERIES OF THREE PATIENTS. INT J MOL SCI. 2025;26(16):1-14. AVAILABLE FROM: HTTPS://DOI.ORG/10.3390/IJMS26168073.FROM THIS PUBLICATION SEVERAL CLUSTERS WERE CREATED.THIS CASE INVOLVES A 59 YEARS OLD FEMALE PATIENT WHO EXPERIENCED CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS (FOREIGN BODY REACTION) (OSTEONECROSIS) AND CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS (SYNOVITIS) WHILE BEING TREATED WITH SYNVISC (LATENCY: UNKNOWN).THE PATIENT'S PAST MEDICAL TREATMENT(S), VACCINATION(S) AND FAMILY HISTORY WERE NOT PROVIDED.PATIENT HAD END-STAGE SEVERE KNEE OA (OSTEOARTHRITIS). FOR SEVERAL YEARS PRIOR TO SURGERY, PATIENTS HAD RECEIVED MULTIPLE INTRA-ARTICULAR INJECTIONS OF VARIOUS (UNSPECIFIED E-HA (EXOGENOUS HYALURONAN) PREPARATIONS (DOSE, FREQUENCY, LOT/BATCH NUMBER AND EXPIRY DATE: UNSPECIFIED).AN UNSPECIFIED TIME LATER, ON AN UNKNOWN DATE, PATIENT EXPERIENCED CHRONIC HYALURONAN-RELATED GRANULOMATOUS SYNOVITIS AND CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS. AREOLAR AND FIBOUS SYNOVIAL MEMBRANE AND SUBCHONDRAL BONE TISSUE SAMPLES WERE AVAILABLE FOR EXAMINATION. PATIENT PRESENTED WITH PERSISTENT CHRONIC PAIN SYNDROME, SIGNIFICANT FUNCTIONAL IMPAIRMENT, AND FAILURE OF CONSERVATIVE TREATMENT. PATIENT UNDERWENT KNEE ARTHROPLASTY FOR END-STAGE SEVERE OA. ACTION TAKEN: UNKNOWN FOR BOTH EVENTSCORRECTIVE TREATMENT: NOT REPORTED FOR BOTH EVENTSOUTCOME: UNKNOWN FOR BOTH EVENTSSERIOUSNESS CRITERIA: MEDICALLY SIGNIFICANT FOR OSTEOMYELITIS CHRONIC; NON SERIOUS FOR SYNOVITISREPORTER CAUSALITY: RELATED FOR BOTH EVENTSA PRODUCT TECHNICAL COMPLAINT (PTC) WAS INITIATED ON 19-SEP-2025 FOR SYNVISC (LOT/BATCH NUMBER: UNKNOWN) WITH GLOBAL PTC NUMBER: COMPLAINT-(B)(4)THE PTC STATED:THE INCIDENT DESCRIPTION, THE INVESTIGATION URGENCY HAS BEEN CONFIRMED AS STANDARD. PER THE PRODUCT-SPECIFIC COMPLAINT CODES FOR "SYNVISC ", AND THE INCIDENT DESCRIPTION, THE DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT" HAS BEEN ASSIGNED TO THIS INVESTIGATION. THE INVESTIGATION URGENCY, QEE/QDN DECISION AND DEFECT CODE MAY CHANGE BASED ON THE OUTCOME OF THE INVESTIGATION. THE MINIMUM INVESTIGATION REQUIREMENTS FOR DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT INCLUDES PRODUCT EVENT HISTORY REVIEW, LOT HISTORY REVIEW, QA BATCH/MANUFACTURING REVIEW (INCLUDING API), THE RESULTS OF THESE REVIEWS ARE SUMMARIZED BELOW:PRODUCT EVENT HISTORY REVIEW:ATTACHMENT 01- COMET PRODUCT (SYNVISC) EVENT HISTORY REPORT FOR THE PAST TWO YEARS WAS GENERATED ON 13-OCT-2025 AND SHOWED 56 COMPLAINTS RELATED TO DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT". ALL THE COMPLAINTS WERE CONCLUDED AS "NO ASSESSMENT POSSIBLE". PRODUCT (SYNVISC) EVENT HISTORY REPORT FOR THE PAST TWO YEARS WAS GENERATED ON 13-OCT-2025 AND SHOWED 166 COMPLAINTS RELATED TO "OTHER PHARMACOVIGILANCE EVENT" (INCLUDING CURRENT COMPLAINT). AMONG THESE"7 COMPLAINTS (INCLUDING CURRENT COMPLAINT) ARE IN OPEN STATE (INVESTIGATION ONGOING)"REVIEW OF EVENT HISTORY REPORT INFERS THAT THERE IS NO CONFIRM COMPLAINT IDENTIFIED, WHICH INCLUDES EVENT IS LINKED TO A FAILURE OR THAT THE DEFECT IS RELATED TO THE PRODUCT OR MANUFACTURING PROCESS. LOT HISTORY REVIEW: AS THE BATCH NUMBER IS UNKNOWN, LOT HISTORY REVIEW AND ASSESSMENT IS NOT POSSIBLE. COMPLAINT SAMPLE EVALUATION: COMPLAINT SAMPLE IS NOT AVAILABLE. HENCE ASSESSMENT IS NOT APPLICABLE. INVESTIGATION OUTCOME:THERE IS NO QUALITY RELATED DEFECT THAT WOULD ATTRIBUTE TO A MALFUNCTION A DEATH OR SERIOUS INJURY. MAH PHARMACOVIGILANCE CONTINUOUSLY MONITORS ADVERSE EVENT REPORTS WITH OR WITHOUT LOT NUMBER, AND ASSESSES POSSIBLE ASSOCIATIONS WITH THEIR CORRESPONDING PRODUCT LOT, AS A PART OF ROUTINE SAFETY SURVEILLANCE EFFORT TO DETECT SAFETY SIGNALS. AS THE PRODUCT LOT NUMBER IS NOT AVAILABLE, A BATCH RECORD REVIEW AND ASSESSMENT IS NOT POSSIBLE. DUE LACK OF INFORMATION, NO ASSESSMENT IS POSSIBLE. CONTROLS IN PLACE:-PRIOR TO BATCH RELEASE, REVIEW OF ALL FINISHED BATCH RECORDS FOR SPECIFICATION CONFORMANCE WILL BE PERFORMED. IF ANY OUT OF SPECIFICATION RESULT IS IDENTIFIED, IT IS MITIGATED THROUGH THE PROCEDURE FOR NONCONFORMING MATERIAL OR PRODUCT PROCESS. -ADVERSE EVENTS WILL BE MONITORED BY THE MAH (MARKETING AUTHORISATION HOLDER) HOLDER. TREND ANALYSIS WILL BE PERFORMED ON A PERIODIC BASIS. TO DETERMINE IF A (CORRECTIVE ACTION AND PREVENTIVE ACTION) IS REQUIRED FOR DEFINED PROCEDURES. TREND ANALYSIS: -PER QU-WIN-0056595, IF THE NUMBER OF COMPLAINTS IS = 10 CONFIRMED COMPLAINTS WITH THE SAME DEFECT CODE FOR THE IMPLICATED PRODUCT IT INDICATES A POTENTIAL TREND FOR THE ASSIGNED DEFECT TYPE. - A CONFIRMED COMPLAINT IS ONE WHERE THE INVESTIGATION HAS CONCLUDED THAT THE REPORTED EVENT IS LINKED TO A FAILURE OR THAT THE DEFECT IS RELATED TO THE PRODUCT OR MANUFACTURING PROCESS. - A REVIEW OF THE PRODUCT EVENT HISTORY REVEALS THAT 222 COMPLAINTS INCLUDING THE CURRENT COMPLAINT FOR PRODUCT SYNVISC WITH DEFECT CODE "OTHER PHARMACOVIGILANCE EVENT" - HOWEVER, REVIEW OF INVESTIGATION CONCLUSIONS INFERS THAT THERE IS NO CONFIRM COMPLAINT IDENTIFIED FOR THE PRODUCT SYNVISC WITH DEFECT "OTHER PHARMACOVIGILANCE EVENT" AND INDICATES THAT NO POTENTIAL TREND (N = 10) EXISTS. - CONSIDERING THE ABOVE FURTHER TREND ANALYSIS OF THE PRODUCT BASED ON THE QUARTERLY DATA IS NOT WARRANTED. CONCLUSION:BASED ON INVESTIGATION OUTCOME, NO QEE WAS OPENED. THE INVESTIGATION URGENCY IS CONFORMED AS STANDARD. AS THE BATCH NUMBER IS NOT AVAILABLE FOR SUBJECT COMPLAINT, NO ASSESSMENT IS POSSIBLE. HENCE INVESTIGATION CONCLUSION IS SELECTED AS "NO ASSESSMENT POSSIBLE" WITH CAUSE CODE AS "UNDETERMINED CAUSE"SANOFI EM&S GEN MED VACCINES QUALITY TEAM WILL CONTINUE TO MONITOR AND TREND THESE TYPES OF EVENTS AND WORK WITH THE CMO(S) TO INITIATE CORRECTIVE AND/OR PREVENTIVE ACTIONS AS NECESSARY. IF ADDITIONAL INFORMATION BECOMES AVAILABLE FOR THIS COMPLAINT, THE INVESTIGATION WILL BE REOPENED AND RE-EVALUATED. THE FINAL PTC WAS COMPLETED ON 13-OCT-2025 WITH SUMMARIZED CONCLUSION AS NO ASSESSMENT POSSIBLE.THE FINAL PTC WAS COMPLETED ON 13-OCT-2025 WITH SUMMARIZED CONCLUSION AS NO ASSESSMENT POSSIBLE.NOTE: PATIENT RECEIPT OF INTRA-ARTICULAR EXOGENOUS HYALURONAN INJECTION. NO EXOGENOUS HYALURONAN BRAND NAME WAS REPORTED; IT IS CAPTURED UNDER THE BRAND SYNVISC IN A CONSERVATIVE APPROACH.ADDITIONAL INFORMATION WAS RECEIVED ON 13-OCT-2025 FROM AFFILIATE AND FOLLOWING CHANGES MADE:PTC RESULT ADDED AND NARRATIVE AMENDED ACCORDINGLY.BASED ON PREVIOUSLY REPORTED INFORMATION WITH CSD 10-SEP-2025, A SIGNIFICANT AMENDMENT HAS BEEN PERFORMED ON 17-OCT-2025 AND THE FOLLOWING CHANGES WERE AMENDED:EVENT CODING ADDED FOR CHRONIC HYALURONAN-RELATED GRANULOMATOUS OSTEOMYELITIS: FOREIGN BODY GRANULOMA (LLT) (PT: FOREIGN BODY REACTION) AND ASEPTIC NECROSIS OF BONE (LLT) (PT: OSTEONECROSIS)
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 2835796 | SYNVISC | MOZ | MOZ | GENZYME CORPORATION(RIDGEFIELD) | UNKNOWN |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 59 YR | Female | Other| R |